Thirst and swallowing represent a fundamental biologic system for the regulation of body water homeostasis. In-utero swallowing, modulated by fetal "thirst" and electrocortical state, results in the resorption of amniotic fluid water, electrolytes and endocrine factors. During the perinatal period, imprinting of hormonal and physiologic factors regulating thirst may permanently alter adult fluid balance. Therefore, the study of fetal "thirst" and swallowing can contribute to an understanding of the development of mechanisms for fluid regulation. In addition, analysis of patterns of esophageal fluid flow and fetal behavioral states may provide insight into the association of neonatal thirst, regurgitation and altered breathing patterns. Spontaneous and thirst-mediated swallowing behavior develop and mature in-utero in sheep and humans. Thus, a fetal model is necessary to investigate the ontogenesis of thirst regulation. We have developed a chronic ovine fetal model for the quantification of swallowing activity and volume and the simultaneous determination of fetal behavioral state. We have demonstrated that, similar to the adult, fetal swallowing both occurs spontaneously and can be stimulated by dipsogenic factors. However, fetal responses to known dipsogenic stimuli may differ from the adult. Furthermore, spontaneous fetal swallowing activity may be suppressed in accordance with behavioral state alterations. This project will characterize the ontogeny of spontaneous fetal swallowing, the presence of diurnal rhythms and the association with fetal behavioral state maturation. The ontogeny of fetal swallowing stimulation by primary systemic stimuli (hyperosmolality and angiotensin II; AII) and the modulation by arginine vasopressin (AVP) and atrial natriuretic factor (ANF) will be studied. The receptor mediation of AII and AVP stimulated swallowing will be probed with selective receptor antagonists. In addition, the central stimulation and suppression of swallowing by primary endocrine factors (AII, AVP, ANF) will be explored. The ovine model offers the opportunity to study, in a precocial species, the ontogeny of "thirst" physiology, an important but relatively unexplored area of perinatal physiology.